CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`APPLICATION NUMBER:
`
`203858Orig1s023
`
`
`
`
`
` JUXTAPID
`Trade Name:
`lomitapide mesylate
`Generic or Proper
`Name:
`
`
`Sponsor:
`
`Approval Date:
`
`Indication:
`
`
`Amryt Pharmaceuticals, Inc
`February 1, 2022
`JUXTAPID is a microsomal triglyceride transfer protein
`inhibitor indicated as an adjunct to a low-fat diet and
`other lipid-lowering treatments, including
`LDL apheresis where available, to reduce low-density
`lipoprotein cholesterol (LDL-C), total cholesterol (TC),
`apolipoprotein B (apo B), and non-highdensity
`lipoprotein cholesterol (non-HDL-C) in patients with
`homozygous familial hypercholesterolemia (HoFH).
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`203858Orig1s023
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Clinical Review(s)
`Product Quality Review(s)
`Non-Clinical Review(s)
`Statistical Review(s)
`Clinical Microbiology / Virology Review(s)
`Clinical Pharmacology Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`
`
`X
`
`
`
`
`
`
`
`
`
`
`
`X
`
`
`
`

`

`
`
`
`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`203858Orig1s023
`
`
`APPROVAL LETTER
`
`

`

`*@ (Bus. Foon & prue
`
`m4 ag 2S:Foo
`
`NDA 203858/S-023
`
`Amryt Pharmaceuticals, Inc.
`US Agent for Amryt Pharmaceutical DAC
`Attention: Karla Werre
`REMS Manager
`160 Federal Street, 21st floor
`Boston, MA 02110
`
`Dear Ms. Werre:
`
`SUPPLEMENT APPROVAL
`
` ÿ
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`
`The REMS for Juxtapid (lomitapide) wasoriginally approved on December21, 2012,
`and the most recent REMS modification was approved on May 27, 2021. The REMS
`consists of elements to assure safe use, an implementation system, and a timetable for
`submission of assessments of the REMS.
`
`Please refer to your supplemental new drug application (SNDA) dated and received
`August 5, 2021, and your amendments, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for Juxtapid (lomitapide) capsules.
`
`This Prior Approval sNDA provides for proposed modifications to the approved Juxtapid
`(lomitapide) risk evaluation and mitigation strategy (REMS).
`
`Wehave completed our review of this supplemental application, as amended. It is
`approved, effective on the date ofthis letter.
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
`
`Your proposed modifications to the REMS consistof:
`
`1. Updating the format of the REMS documentin line with the recommendationsin
`the Format and Content of a REMS Document- Guidancefor Industry’
`
`2. Changesto program materials secondary to findings of the completed Qualitative
`Research (QR) aroundthe deficit of prescriber knowledge on program
`requirements around liver monitoring as demonstrated in recent poor KAB survey
`scores
`
`1We update guidancesperiodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Databasehttps://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`Reference ID: 4930852
`
`

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`

`NDA 203858/S-023
`Page 4
`
`Program Patient-Prescriber Acknowledgement Form.
`
`iil.
`
`iv.
`
`Number of instancescertified pharmacies dispensed Juxtapid in
`responseto a prescription received on an altered Juxtapid REMS
`Program Prescription Authorization Form.
`
`The number of newprescriptions received, and the number that
`were not accompanied by the Juxtapid REMS Program Prescription
`Authorization Form.
`
`d. Wholesalers/Distributors
`
`i.
`
`ii.
`
`Number of wholesalers/distributors that had their authorization
`revoked during the reporting period and cumulatively and the reason
`for the revocation.
`
`Number of Juxtapid orders shipped to non-certified pharmacies.
`
`3. REMS Call Center
`
`a. Summary of issues and complaints received by Juxtapid REMS Program Call
`Center; summary of resolution of the issues and complaints.
`
`Summary of the reasons (and numbersper reason) for calls into the Juxtapid
`REMS Program Call Center.
`
`4. Juxtapid Utilization Data
`
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`
`a. The numberof prescriptions dispensed for Juxtapid, including quantity of
`capsules (mean, minimum, maximum) and dosagestrength, overall and
`subset by compliance with the Juxtapid REMS Program requirements(e.g.,
`received from Juxtapid certified vs. non-certified healthcare providers, number
`ofinitial prescriptions dispensed without a signed attestation on the Juxtapid
`REMSProgram Prescription Authorization Form). Dispensing details are to
`be obtained from the pharmacies.
`
`. Volumeof prescriptions for each prescriberstratified by specialty, including a
`full breakdownof prescribing specialties contained in the “other” category.
`
`. Specialties of the “high volume”prescribers, i.e., those who write more than
`four prescriptions in an assessmentperiod and cumulatively, including a full
`breakdownofprescribing specialties contained in the “other” category.
`
`. The numberof Juxtapid orders shipped to pharmacies during the reporting
`period and cumulatively, including numberof bottles, bottle size and dosage
`strength.
`
`. The number and demographics(e.g., including gender, age, geographic
`location) of unique patients who received Juxtapid during the reporting period
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4930852
`
`

`

`NDA 203858/S-023
`Page 5
`
`and annually. The number is to be calculated by reconciling orders dispensed
`to unique patients.
`
`f. Duration of therapy for patients (mean, median, range).
`
`g. The numberof prescriptions pending and canceled, as well as the reason for
`prescriptions pending and canceled.
`
`h. Specific criterion used to classify a prescription as canceled.
`
`i. Report of number, length, and reasonsfor shipment delays to patients and
`whetheror not these reasonswere related to the REMS, and anyadditional
`information from insurance payersas to what they are stating as the reason
`for delay/non-payment.
`
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`j.
`
`Percentageoffill delays that involve new prescriptions versusrefills.
`
`Knowledge(per reporting period and cumulatively)
`
`5. Knowledge, Attitudes, and Behavior (KAB) Surveys of Prescribers to assess
`understandingof:
`
`a. The approvedindication of Juxtapid
`
`b. The risk of hepatoxicity associated with Juxtapid use
`
`c. The need to monitor patients during treatment with Juxtapid as per product
`labeling
`
`6. Survey to Evaluate Patient Knowledgeof:
`
`a.
`
`b.
`
`the risk of hepatoxicity
`
`the need for baseline and periodic monitoring
`
`7. Specification of measures that would be taken to increase awarenessif surveys
`indicate that awarenessofthe risks associated to Juxtapid is not adequate.
`
`Safe Use Conditions (per reporting period and cumulatively)
`
`8. Prescription Authorization Form (PAF)
`
`a. Number of patients with completed PAFs who havenotreceived a dispensed
`prescription for Juxtapid.
`
`b. Time betweenreceipt of PAF and prescription dispensing and analysis and
`summary of reasonsfor delays
`
`c. Proportion of prescriptions that were associated with the updated PAF from
`the February 2022 REMS modification.
`
`9. Patient-Prescriber Acknowledgement Form (PPAF)
`
`a. Proportion of dispensed prescriptions associated with an updated PPAF from
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4930852
`
`

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`

`NDA 203858/S-023
`Page 9
`
`REPORTING REQUIREMENTS
`
`Weremind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`If you have any questions, call Ron Picking, Regulatory Project Manager,at
`240-402-3211.
`
` ÿ
`ÿ
`

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`
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`
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`
`ENCLOSURES:
`Juxtapid REMS Document
`Juxtapid REMS Materials:
`¢ Prescriber Enrollment Form
`¢ Patient Guide
`¢ Patient-Prescriber Acknowledgement Form
`¢ Prescription Authorization Form
`¢ Pharmacy Enrollment Form
`¢ Prescriber Training Module and Knowledge Assessment
`¢ Pharmacy Training Module and Knowledge Assessment
`¢ Fact Sheet
`¢ Website
`
`Sincerely,
`
`{See appendedelectronic signature page}
`
`Monika Houstoun, Pharm.D., M.P.H.
`Deputy Director for Safety (Acting)
`Division of Diabetes, Lipid Disorders, and
`Obesity
`Office of Cardiology, Hematology,
`Endocrinology, and Nephrology
`Center for Drug Evaluation and Research
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4930852
`
`

`

`Signature Page 1 of 1
`
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any andall
`electronic signatures for this electronic record.
`
`
`ÿÿÿÿ ÿÿ!""ÿ"#ÿÿ$ÿ%#ÿ
`!""!!&'ÿ(!!$%ÿÿÿ) ÿ ÿ&ÿ#ÿ!!ÿ
`
`

ÿ
`ÿÿÿÿ
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`
`+,+ÿ-./012ÿ2ÿ3.45.4/ÿ
`
`67+6+7677ÿ68798:;ÿ-ÿ
`
` ÿ
`
`MONIKA A HOUSTOUN
`02/01/2022 10:25:47 PM
`
`Reference ID: 4930852
`
`<=>=?=@A=ÿCDEÿFGHIJKLÿ
`
`

`

`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`203858Orig1s023
`
`
`REMS
`DOCUMENTS
`
`

`

`Risk Evaluation and Mitigation Strategy (REMS) Document
`JUXTAPID (lomitapide) REMS Program
`
`I. Administrative Information
`Application Number:
`NDA 203858
`Application Holder:
`Amryt Pharmaceuticals DAC
`Initial REMS Approval:
`12/2012
`Most Recent REMS Update: 02/2022
`
`II. REMS Goal
`The goal of the JUXTAPID REMS is to mitigate the risk of hepatotoxicity associated with the use
`of JUXTAPID by ensuring that:
`
`(cid:120)
`
`(cid:120)
`
`(cid:120)
`
`Prescribers are educated about the approved indication for JUXTAPID, the risk of
`hepatotoxicity associated with the use of JUXTAPID; and the need to monitor patients
`during treatment with JUXTAPID as per product labeling.
`JUXTAPID is dispensed only to patients with a clinical or laboratory diagnosis
`consistent with homozygous familial hypercholesterolemia (HoFH).
`Patients are informed about the risk of hepatotoxicity associated with the use of
`JUXTAPID and the need for baseline and periodic monitoring.
`
`III. REMS Requirements
`Amryt Pharmaceuticals DAC must ensure that healthcare providers, patients,
`pharmacies, and wholesalers-distributors comply with the following requirements:
`
`1. Healthcare Providers who prescribe JUXTAPID must:
`
`To become
`certified to
`prescribe
`
`Before treatment
`initiation (first
`dose)
`
`1. Review the drug’s Prescribing Information.
`2. Review the following: Fact Sheet, Prescriber Training Module.
`3. Successfully complete the Knowledge Assessment and submit it to
`the REMS Program.
`4. Enroll in the REMS by completing the Prescriber Enrollment Form and
`submitting it to the REMS Program.
`
`5. Counsel the patient about the appropriate use, risks associated with
`JUXTAPID, and need for periodic liver function monitoring using the
`Patient Guide. Provide a copy of the material to the patient.
`6. Assess the patient to confirm a clinical or laboratory diagnosis
`consistent with the approved indication.
`7. Assess the patient’s liver function.
`8. Enroll the patient by completing and submitting the Patient-
`Prescriber Acknowledgement Form to the REMS Program.
`
`Reference ID: 4930852
`
`

`

`1. Healthcare Providers who prescribe JUXTAPID must:
`9. Order the prescription using the Prescription Authorization Form.
`
`During treatment,
`at least monthly
`for the first year
`and every 3
`months thereafter
`During treatment,
`before dose
`increases
`
`During treatment;
`before each
`prescription
`
`10. Assess the patient’s liver function.
`
`11. Assess the patient’s liver function.
`
`12. Order the prescription using the Prescription Authorization Form.
`
`2. Patients who are prescribed JUXTAPID:
`
`Before treatment
`initiation
`
`1. Receive counseling from the prescriber on the appropriate use, risks
`of JUXTAPID, and need for periodic liver function monitoring using
`the Patient Guide.
`2. Enroll in the REMS Program by completing the Patient-Prescriber
`Acknowledgement Form with the prescriber. Enrollment information
`will be provided to the REMS Program.
`3. Get blood tests to check your liver.
`
`During treatment
`
`4. Get blood tests as directed by your prescriber to check your liver so
`your prescriber can modify your JUXTAPID treatment, if needed.
`
`At all times
`
`5. Inform the prescriber of signs and/or symptoms of liver injury.
`
`3. Pharmacies that dispense JUXTAPID must:
`
`To become
`certified to
`dispense
`
`1. Designate an authorized representative to carry out the certification
`process and oversee implementation and compliance with the REMS
`Program on behalf of the pharmacy.
`
`2. Have the authorized representative review the Prescribing
`Information, Fact Sheet and Pharmacy Training Module.
`
`3. Have the authorized representative successfully complete the
`Knowledge Assessment and submit it to the REMS Program.
`4. Have the authorized representative enroll in the REMS Program by
`completing the Pharmacy Enrollment Form and submitting it to the
`REMS Program.
`
`Reference ID: 4930852
`
`

`

`3. Pharmacies that dispense JUXTAPID must:
`5. Establish processes and procedures to verify the prescriber is
`certified, the patient is enrolled, and a completed Prescription
`Authorization Form is received for each prescription.
`6. Train all relevant staff involved in dispensing of JUXTAPID on the
`REMS Program requirements.
`
`Before dispensing
`
`To maintain
`certification to
`dispense
`
`At all times
`
`7. Verify that the prescriber is certified, the patient is enrolled, and a
`completed Prescription Authorization Form for the patient is received
`for each prescription through the processes and procedures
`established as a requirement of the REMS Program.
`
`8. Have a new authorized representative enroll by completing and
`submitting the Pharmacy Enrollment Form, if the authorized
`representative changes.
`
`9. Not distribute, transfer, loan, or sell JUXTAPID.
`10. Maintain records documenting staff’s completion of REMS training.
`11. Maintain and submit records of prescription data to the REMS
`Program.
`12. Maintain records that all REMS processes and procedures are in place
`and are being followed.
`13. Comply with audits carried out by Amryt Pharmaceuticals DAC or a
`third-party acting on behalf of Amryt Pharmaceuticals DAC, to
`ensure that all processes and procedures are in place and are being
`followed.
`
`4. Wholesalers-distributors that distribute JUXTAPID must:
`
`To be able to
`distribute
`
`At all times
`
`1. Establish processes and procedures to ensure the drug is distributed
`only to certified pharmacies.
`2. Train all relevant staff involved in distributi